Cancer Genomics & Proteomics最新文献

{"title":"γ-Glutamylcyclotransferase Depletion Induces p15^INK4b and p21^Cip1-mediated Senescence <i>via</i> TGF-β2/SMAD3 Pathway Activation in Breast Cancer Cells.","authors":"Shigehisa Kubota, Hiromi Ii, Takahiro Isono, Takuto Kusaba, Masayuki Nagasawa, Akinori Wada, Kenichi Kobayashi, Kazuaki Yamanaka, Masaya Mori, Keiko Taniguchi, Susumu Nakata, Susumu Kageyama","doi":"10.21873/cgp.20571","DOIUrl":"10.21873/cgp.20571","url":null,"abstract":"<p><strong>Background/aim: </strong>γ-Glutamylcyclotransferase (GGCT) depletion suppresses breast cancer cell proliferation by inducing cellular senescence. However, the underlying molecular mechanisms have not been fully elucidated. Therefore, the objective of this study was to elucidate the mechanisms by which GGCT depletion suppresses cancer cell proliferation.</p><p><strong>Materials and methods: </strong>Human breast cancer MCF-7 cells were transfected with GGCT-specific or control siRNAs. Transcriptomic profiling by RNA sequencing identified differentially expressed genes (<i>q</i><0.01, |log₂ fold change|>1), and Gene Ontology and KEGG analyses characterized affected pathways. Key genes and functional effects on the TGF-β2/SMAD3 axis, cell-cycle progression, and senescence were validated by qRT-PCR, western blotting, and SA-β-Gal assays.</p><p><strong>Results: </strong>Comprehensive gene expression analysis revealed that depletion of <i>GGCT</i> increases the expression levels of the cell cycle arrest factors <i>CDKN1A</i> (p21^Cip1) and <i>CDKN2B</i> (p15^INK4b), accompanied by elevated transforming growth factor-β2 (<i>TGFB2</i>) expression. Blocking this pathway through the simultaneous knockdown of <i>TGFB2</i> was found to significantly restore the growth-inhibitory effect mediated by cellular senescence induced by <i>GGCT</i> depletion. This finding demonstrated that these phenotypes depend on the TGF-β2 pathway. Furthermore, we identified SMAD3 as a TGF-β2 downstream factor essential for the increase in p21^Cip1 and p15^INK4b and the growth-inhibitory effect induced by GGCT depletion.</p><p><strong>Conclusion: </strong>Activation of the TGF-β2/SMAD3 pathway is a mechanism by which cellular senescence is induced through GGCT depletion, suggesting that GGCT inhibition represents a promising therapeutic strategy for the treatment of breast cancer.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 2","pages":"195-209"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12951391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147343291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NPM1 Drives ERK1/2-dependent Tumor Progression in Lung Cancer.","authors":"Hong-Beum Kim, Hee-Jeong Lee, Sang-Gon Park","doi":"10.21873/cgp.20572","DOIUrl":"10.21873/cgp.20572","url":null,"abstract":"<p><strong>Background/aim: </strong>Lung cancer is the most lethal malignancy worldwide, and there remains an urgent need for reliable biomarkers to improve diagnosis and treatment. Nucleophosmin 1 (NPM1), a nucleolar phosphoprotein, has been implicated in hematological cancers, but its significance in lung cancer is less clear. This study investigated the oncogenic role of NPM1 in lung cancer and its involvement in ERK1/2 pathway activation in lung cancer cells.</p><p><strong>Materials and methods: </strong>Transcriptomic data from TCGA were analyzed to assess NPM1 expression in lung cancer and normal tissues. <i>In vitro</i> assays using A549 and H1299 cells were conducted following siRNA-mediated silencing of NPM1. Cell proliferation, soft agar colony formation, and western blot analyses were performed. <i>In vivo</i> tumorigenicity was tested using a nude mouse xenograft model.</p><p><strong>Results: </strong>NPM1 expression was significantly elevated in lung cancer tissues compared with normal samples. Silencing NPM1 reduced proliferation, colony formation, and tumor growth. Mechanistic studies revealed that NPM1 knockdown decreased phosphorylation of ERK1/2, indicating its role in activating this pathway.</p><p><strong>Conclusion: </strong>NPM1 contributes to lung cancer progression <i>via</i> ERK1/2 signaling. These results highlight NPM1 as a novel oncogene and suggest its potential as a diagnostic and prognostic biomarker in lung cancer.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 2","pages":"210-219"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12951369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147343299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SNRPD2-dependency Fuels an Oncogenic Alternative Splicing Repertoire Driving Disease Aggressiveness in Glioma.","authors":"Dayu Li, Jinshan Wang, Guofeng Zhang, Emily Shang, Farhana Akter, Jiaming Wang, Xingping Qin, Haipeng Liu, Ailiang Zeng, Shun Yao, Yanmei Tie, Kashif Rafiq Zahid, Shaolei Guo","doi":"10.21873/cgp.20570","DOIUrl":"10.21873/cgp.20570","url":null,"abstract":"<p><strong>Background/aim: </strong>Gliomas are the most common primary brain tumors, yet the molecular circuits that drive their malignancy remain incompletely defined. Here, using an integrative, multi-dimensional approach, we aimed to pinpoint key molecular drivers having both functional and clinical relevance to disease progression and tumor aggressiveness in gliomas.</p><p><strong>Materials and methods: </strong>Genome-wide CRISPR-Cas9 dependency screen across 70 glioma cell lines was paired with tumor aggressiveness-targeted transcriptomic differential expression and survival analyses to pinpoint critical drivers of disease progression in gliomas. Functional and gene set enrichments as well as protein-protein interaction network analyses were used to identify dominant pathways and key hub genes, followed by independent validation across external transcriptomic and proteomic datasets. Upstream regulator analyses and alternative splicing profiling were performed to nominate regulatory drivers and derive a small nuclear ribonucleoprotein D2 polypeptide (SNRPD2)-associated splicing signature.</p><p><strong>Results: </strong>Initial screening uncovered 222 essential genes (Chronos<-1) in gliomas, 87 of which were overexpressed in tumors displaying proliferative, epithelial-mesenchymal transition, glycolytic, hypoxic, and inflammatory signatures, and were associated with poor overall survival, consistent with aggressive disease biology. These genes converged on alternative splicing regulation, proteasome function, and cell cycle, with spliceosome core component, SNRPD2 emerging as the top hub gene. High SNRPD2 expression was associated with disease aggressiveness, tumor progression, and adverse clinical outcomes. MYC was identified as a putative transcriptional driver of SNRPD2. High SNRPD2 expression was also linked to differential (oncogenic) alternative splicing of multiple cancer-associated genes, correlating with disease aggressiveness and poor clinical outcomes.</p><p><strong>Conclusion: </strong>These data establish SNRPD2 and its associated alternatively spliced repertoire as a central adaptive node linked to disease aggressiveness in gliomas, highlighting it as a potential therapeutic target in glioma patients.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 2","pages":"169-194"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12951373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147343283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibronectin 1 (<i>FN1</i>)-rearranged Mesenchymal Neoplasms: An Updated Review.","authors":"Jun Nishio, Yoshiro Chijiiwa, Yuki Shinohara, Mikiko Aoki, Kaori Koga","doi":"10.21873/cgp.20569","DOIUrl":"10.21873/cgp.20569","url":null,"abstract":"<p><p>Fibronectin 1 (<i>FN1</i>), located on chromosome 2q35, encodes fibronectin, a high molecular weight glycoprotein of the extracellular matrix. Several histologically overlapping chondroid matrix-producing tumors are known to harbor <i>FN1</i> rearrangements, including soft tissue chondroma, synovial chondromatosis, calcifying aponeurotic fibroma, calcified chondroid mesenchymal neoplasm and phosphaturic mesenchymal tumor. Over the past 10 years, fusions involving the <i>FN1</i> gene have also been identified in other mesenchymal neoplasms such as lipofibromatosis and inflammatory myofibroblastic tumor. The current World Health Organization Classification of Soft Tissue and Bone Tumors suggests that <i>FN1</i>-rearranged lesions are typically benign or intermediate. This review provides an updated overview of the clinical, histological and molecular genetic features of <i>FN1</i>-rearranged mesenchymal neoplasms and discusses their relationships with one another.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 2","pages":"156-168"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12951374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147343732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-expression of <i>PKCζ</i> and <i>ALDH1A3</i> Is Associated With Poor Chemotherapeutic Responses in Basal-like Breast Cancer.","authors":"Yuka Nagashima, Megumi Ogino, Ranman Okiyama, Ryosuke Chiwaki, Hayato Ishii, Kana Nohata, Ayaka Nakahara, Ayaka Ozaki, Takahiro Kasai, Shoma Tamori, Shigeo Ohno, Kazunori Sasaki, Kazunori Akimoto","doi":"10.21873/cgp.20579","DOIUrl":"10.21873/cgp.20579","url":null,"abstract":"<p><strong>Background/aim: </strong>The association between the expression of protein kinase C zeta (<i>PKCζ</i>) and chemotherapeutic responses among different subtypes of breast cancer has yet to be fully elucidated. The present study aimed to investigate the association between <i>PKCζ</i> expression and disease-specific survival (DSS) rates, with a particular focus on the influence of chemotherapy and cancer stem cell (CSC)-associated <i>ALDH1A3</i> expression.</p><p><strong>Materials and methods: </strong>Clinical and gene expression data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset (n=2,509) were analyzed using Kaplan-Meier and Cox proportional hazards models. The findings were validated using The Cancer Genome Atlas (TCGA) Pan-Cancer Atlas dataset (n=1,084).</p><p><strong>Results: </strong>In the METABRIC dataset, high <i>PKCζ</i> expression (<i>PKCζ</i> ^high) was associated with poor DSS rates in patients with the normal-like, claudin-low and basal-like subtypes treated with chemotherapy. Consistent results were obtained in TCGA dataset, where <i>PKCζ</i> ^high expression in basal-like breast cancer predicted poor prognosis, especially among patients treated with cyclophosphamide, an alkylating agent. Combined analysis further revealed that patients with high expression of both <i>PKCζ</i> and <i>ALDH1A3</i> (<i>PKCζ</i> ^high/<i>ALDH1A3</i> ^high) basal-like tumors treated with cyclophosphamide, doxorubicin, or fluorouracil had the worst DSS rates compared with other groups. In addition, <i>PKCζ</i> ^high/<i>ALDH1A3</i> ^high basal-like tumors treated with anthracycline- or taxane-based regimens also exhibited poorer prognoses compared with other groups.</p><p><strong>Conclusion: </strong><i>PKCζ</i> contributes to chemotherapeutic resistance, especially in patients with <i>ALDH1A3</i>-positive basal-like breast cancer, possibly through the regulation of CSC survival and proliferation. Moreover, <i>PKCζ</i>, either alone or in combination with <i>ALDH1A3</i> expression, may serve as a prognostic biomarker for predicting the therapeutic efficacy of chemotherapy in basal-like breast cancer.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 2","pages":"322-341"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12951394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147343684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Timescale-dependent Phosphoproteomic Remodeling and Motility-associated Adaptation under Chronic Cabozantinib Exposure in Renal Cell Carcinoma.","authors":"Shao-Kuan Chen, Yen-Chieh Wang, Yu-Heng Hsieh, Chi-Jung Huang, Wei-Chi Ku","doi":"10.21873/cgp.20576","DOIUrl":"10.21873/cgp.20576","url":null,"abstract":"<p><strong>Background/aim: </strong>Cabozantinib is a multi-target tyrosine kinase inhibitor used in renal cell carcinoma (RCC), yet the exposure-dependent remodeling of phosphorylation networks under short-term <i>versus</i> chronic treatment remains insufficiently defined. This study applied quantitative phosphoproteomics to delineate remodeling programs induced by acute and chronic cabozantinib exposure and to examine cellular features within the same signaling background.</p><p><strong>Materials and methods: </strong>RCC cells were subjected to acute (48 h) or chronic (>4-month) cabozantinib exposure. Dimethyl-labeling-based phosphoproteomics was used to quantify phosphosites and derive pathway- and kinase-substrate-level modules, integrated with functional enrichment, 2D-annotation and PTM-signature analyses, immunoblotting, migration, and Matrigel invasion assays.</p><p><strong>Results: </strong>A total of 6,305 phosphosites were quantified. Acute cabozantinib exposure predominantly downregulated cell-cycle and CDK-associated phosphorylation, consistent with a broad cytostatic remodeling pattern, whereas chronic cabozantinib exposure produced a more selective redistribution enriched for adhesion- and stress-associated modules, including MAPK/AP-1/MAPKAPK2/HSPB1-linked signatures. Activation-loop MET phosphorylation (Y1234/1235) remained suppressed under both exposure conditions, while phosphorylation of MET at T977 increased under chronic cabozantinib treatment and was interpreted as site-specific regulation within the remodeled phosphorylation context rather than restoration of MET signaling activity. Motility features examined in the same cellular background showed pattern-specific differences: migration exhibited modest but significant increases with a larger effect size in chronically cabozantinib-exposed cells under drug treatment, whereas invasion was consistently higher in chronically cabozantinib-exposed cells than in parental cells across conditions without a marked treatment-specific change.</p><p><strong>Conclusion: </strong>Chronic cabozantinib exposure is characterized by sustained suppression of MET phosphorylation and a selective adhesion- and MAPK/AP-1-associated phosphorylation program, accompanied by modest, pattern-specific motility differences observed within the same signaling context. These findings provide a systems level framework for future mechanistic and <i>in vivo</i> evaluation.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 2","pages":"265-280"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12951389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147343342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ATIC Knockdown Reduces B7-H3 Expression and Oncogenic Signaling in Upper Tract Urothelial Carcinoma Cells.","authors":"Hung-Lung Ke, Wei-Chi Hsu, Yin-Lun Chang, Jhen-Hao Jhan, Yi-Yang Liu, Che-Wei Chang, Hui-Hui Lin, A-Mei Huang, Yi-Ru Wu, Hao-Lun Luo, Hui-Ying Liu","doi":"10.21873/cgp.20575","DOIUrl":"10.21873/cgp.20575","url":null,"abstract":"<p><strong>Background/aim: </strong>Upper tract urothelial carcinoma (UTUC) has a notably high incidence and aggressiveness in East Asian populations; however, its molecular mechanisms remain poorly defined. Our previous study identified 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC), a bifunctional enzyme involved in <i>de novo</i> purine biosynthesis, as a tumor-promoting factor regulated by microRNA-145-5p in UTUC. Therefore, this study aimed to systematically investigate the functional interplay between ATIC and its downstream effectors in UTUC.</p><p><strong>Materials and methods: </strong>To elucidate ATIC-regulated signaling pathways, we performed tandem mass tag (TMT)-based quantitative proteomics in BFTC909 cells with ATIC knockdown, followed by functional, biochemical, and drug-sensitivity assays.</p><p><strong>Results: </strong>Proteomic profiling identified B7-H3 (CD276), prion protein (PRNP), RAC2, and NT5E (CD73) as downstream molecules downregulated by ATIC silencing. Functional assays revealed that suppressing the expression of these proteins inhibited cell proliferation, migration, and invasion, and enhanced cisplatin sensitivity. RNA interference analysis indicated that B7-H3 may lie upstream of prion protein and RAC2. Mechanistically, the ATIC/B7-H3 axis were shown to modulate mTOR, AKT, ERK, and p38 phosphorylation, linking metabolic activity to oncogenic and chemoresistant signaling.</p><p><strong>Conclusion: </strong>These findings revealed an ATIC-associated metabolic-immunoregulatory network in UTUC, through which ATIC supports mTOR-related signaling and promotes tumor progression and cisplatin resistance. Targeting the ATIC-driven network may offer new therapeutic opportunities for UTUC management.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 2","pages":"244-264"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12951375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147343726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding the Mechanisms of Hepatocellular Carcinoma Cancer Stem Cells and Identifying Potential Therapeutic Strategies Based on Single-cell Omics.","authors":"Xiaotian Tan, Qiaoxian Luo, Ying Ge, Ning Deng, Ping Jin, Menghuan Song, Carolina Oi Lam Ung, Meiwan Chen, Hao Hu","doi":"10.21873/cgp.20577","DOIUrl":"10.21873/cgp.20577","url":null,"abstract":"<p><strong>Background/aim: </strong>Cancer stem cells (CSCs) play key roles in hepatocellular carcinoma (HCC) initiation, progression, therapeutic resistance, and recurrence, yet their cellular and spatial heterogeneity remains poorly understood. This study aimed to systematically characterize HCC-associated CSCs and identify prognostic biomarkers and potential therapeutic strategies using single-cell omics.</p><p><strong>Materials and methods: </strong>Single-cell RNA sequencing and spatial transcriptomics data were obtained from HCCDB v2.0. Malignant cells were re-clustered using Harmony-based batch correction, followed by uniform manifold approximation and projection (UMAP) and Louvain clustering. Copy number variation analysis validated malignant identities. CSC-associated molecular features were characterized using differential expression, gene regulatory network analysis (SCENIC), pathway enrichment (GSVA), pseudotime trajectory inference (Monocle, CytoTRACE2), and cell-cell communication analysis (CellChat). CSC-specific genes were integrated with GEO survival datasets (GSE76427, GSE14520) to construct a prognostic model, and potential CSC-targeting compounds were predicted using Connectivity Map.</p><p><strong>Results: </strong>Six malignant subpopulations were identified, including a progenitor-like CSC subset expressing EPCAM, SOX9, and SOX4. Spatial transcriptomics revealed CSC enrichment at the tumor-stroma interface. CSCs exhibited strong stemness, metabolic plasticity, and invasive potential, with activation of WNT/β-catenin, TGF-β, Notch, EMT, MYC, and mTORC1 pathways. Key transcription factors (TEAD2, SOX4, HNF1B, KLF7) were identified. A 12-gene CSC-derived signature stratified patients into distinct risk groups with significantly different overall survival. Several candidate compounds, including fluspirilene, genistein, and daunorubicin, showed potential CSC-suppressive activity.</p><p><strong>Conclusion: </strong>This study provides a comprehensive single-cell-based atlas of CSCs in HCC, highlighting their spatial niches, regulatory programs, and clinical relevance. The identified prognostic signature and candidate drugs offer promising avenues for CSC-targeted therapies.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 2","pages":"281-299"},"PeriodicalIF":2.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12951371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147343729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low <i>CTDNEP1</i> Expression Predicts Poor Prognosis and Is Associated With Immune Modulation in Pancreatic Cancer.","authors":"Mayuka Nii, Tadayoshi Hayata","doi":"10.21873/cgp.20567","DOIUrl":"10.21873/cgp.20567","url":null,"abstract":"<p><strong>Background/aim: </strong>Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy due to limited therapeutic options. Identifying novel genes that influence its progression is critical. This study aimed to investigate the role of <i>CTDNEP1</i>, a phosphatase-encoding gene, in PDAC using multi-omics data from The Cancer Genome Atlas (TCGA).</p><p><strong>Materials and methods: </strong>We analyzed <i>CTDNEP1</i> expression in PDAC using the TCGA and Pan-Cancer Atlas datasets. Kaplan-Meier survival analysis was performed to assess the association between <i>CTDNEP1</i> expression and patient prognosis. Gene Ontology (GO) and KEGG pathway enrichment analyses were conducted to explore the biological processes linked to <i>CTDNEP1</i> expression. Finally, we examined the relationship between <i>CTDNEP1</i> expression and the tumor immune microenvironment using immune infiltration analysis.</p><p><strong>Results: </strong><i>CTDNEP1</i> expression was found to be significantly lower in PDAC tissues compared to normal tissues, especially in early-stage tumors. This downregulation was associated with mutations in key driver genes, including <i>KRAS, CDKN2A, TP53</i>, and <i>SMAD4</i>. Importantly, low <i>CTDNEP1</i> expression correlated with significantly poorer patient prognosis, particularly in stage II PDAC. Functional enrichment analysis revealed that low <i>CTDNEP1</i> expression is associated with macroautophagy, protein degradation, and immune/inflammatory pathways, while high expression is linked to mitochondrial function and metabolic activity. Furthermore, <i>CTDNEP1</i> expression showed a positive correlation with immune cell infiltration.</p><p><strong>Conclusion: </strong><i>CTDNEP1</i> functions as a tumor suppressor in PDAC, influencing tumor progression, immune response, and patient survival. Future studies should investigate the detailed regulatory mechanisms of <i>CTDNEP1</i> and explore its potential as a therapeutic target or biomarker for PDAC.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 1","pages":"144-154"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12758660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA Damage-induced Post-transcriptional Regulation of SIRT4 by the miR-15/16 Family Modulates Chemosensitivity in Cancer Cells.","authors":"Sangyeon Won, Minbeom Ko, Seung Min Jeong","doi":"10.21873/cgp.20562","DOIUrl":"10.21873/cgp.20562","url":null,"abstract":"<p><strong>Background/aim: </strong>SIRT4 is a mitochondrial regulator of metabolism and stress responses, yet the mechanisms underlying its induction upon DNA damage remains unclear. This study aimed to define the mechanism of SIRT4 regulation and the role of the miR-15/16 family in this process.</p><p><strong>Materials and methods: </strong>SIRT4 expression was examined after DNA-damaging treatments in MEFs and HeLa cells. Reporter assays, mRNA decay analysis, and mutagenesis of the SIRT4 3'UTR were performed to identify regulatory mechanisms. Gain- and loss-of-function studies assessed the involvement of the miR-15/16 family. Cell viability was evaluated.</p><p><strong>Results: </strong>SIRT4 was strongly induced by DNA damage and required for cell survival under genotoxic stress. This induction occurred through mRNA stabilization with the 3'UTR of SIRT4 serving as the determinant of stability. The miR-15/16 family targeted a conserved site within the SIRT4 3'UTR to destabilize its mRNA. Overexpression of miR-15/16 reduced SIRT4 expression and sensitized cells to chemotherapy.</p><p><strong>Conclusion: </strong>The miR-15/16-SIRT4 axis represents a novel mechanism of post-transcriptional regulation in the DNA damage response and may serve as a therapeutic target to improve the efficacy of chemotherapy.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"23 1","pages":"81-92"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12758664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}